title: Enhanced killing of therapy-induced senescent tumor cells by oncolytic measles vaccine viruses.
abstract: Therapy-induced senescence (TIS) as a permanent growth arrest can be induced by various stimuli, including anticancer compounds. TIS emerged as a promising strategy to overcome resistance phenomena. However, senescent cancer cells might regain proliferation activity in vivo or even secrete tumor-promoting cytokines. Therefore, successful exploitation of TIS in cancer treatment simultaneously requires the development of effective strategies to eliminate senescent cancer cells. Virotherapy aims to selectively hit tumor cells, thus a combination with senescence-inducing drugs was explored. As a model, we chose measles vaccine virus (MeV), which does not interfere with cellular senescence by itself. In different tumor cell types, such as hepatoma, pancreatic and mammary gland carcinoma, we demonstrate efficient viral replication and lysis after TIS by gemcitabine, doxorubicin or taxol. Applying real time imaging, we even found an accelerated lysis of senescent cancer cells, supporting an enhanced viral replication with an increase in cell-associated and released infectious MeV particles. In summary, we show as a proof-of-concept that senescent tumor cells can be efficiently exploited as virus host cells by oncolytic MeV. These observations open up a new field for preclinical and clinical research to further investigate TIS and oncolytic viruses as an attractive combinatorial future treatment approach.
authors.affiliation: Department of Internal Medicine I, Medical University Hospital, University of Tübingen, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Weiland
authors.forename: Johanna
authors.initials: J
authors.lastname: Lampe
authors.forename: Frank
authors.initials: F
authors.lastname: Essmann
authors.forename: Sascha
authors.initials: S
authors.lastname: Venturelli
authors.forename: Alexander
authors.initials: A
authors.lastname: Berger
authors.forename: Sascha
authors.initials: S
authors.lastname: Bossow
authors.forename: Susanne
authors.initials: S
authors.lastname: Berchtold
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.forename: Michael
authors.initials: M
authors.lastname: Bitzer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D008458:Measles Vaccine / Q000627:therapeutic use; D008459:Measles virus / Q000502:physiology*; D009369:Neoplasms / Q000628:therapy / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D008458:Measles Vaccine
keywords: breast cancer; hepatoma; pancreatic cancer; therapy-induced senescence; virotherapy